Breaking barriers: How modified citrus pectin inhibits galectin-8.

Inhibition of galectin-3-mediated interactions by modified citrus pectin (MCP) could affect several rate-limiting steps in cancer metastasis, but the ability of MCP to antagonize galectin-8 function remains unknown. We hypothesized that MCP could bind to galectin-8 in addition to galectin-3. In this study, a combination of gradual ethanol precipitation and DEAE-Sepharose Fast Flow chromatography was used to isolate several fractions from MCP. The ability of these fractions to antagonize galectin-8 function was studied as well as the primary structure and initial structure-function relationship of the major active component MCP-30-3. The results showed that MCP-30-3 (168 kDa) was composed of Gal (13.8%), GalA (63.1%), GlcA (13.0%), and Glc (10.1%). MCP-30-3 could specifically bind to galectin-8, with an MIC value of 0.04 mg mL-1. After MCP-30-3 was hydrolyzed by ß-galactosidase or pectinase, its binding activity was significantly reduced. These results provide new insights into the interaction between MCP structure and galectin function, as well as the potential utility in the development of functional foods.

Exploring the effects of calycosin on anthracycline-induced cardiotoxicity: a network pharmacology, molecular docking, and experimental study.

Background: Chemotherapy with anthracyclines can cause cardiotoxicity, possibly leading to stopping treatment in some cancer patients. In cardio-oncology research, preventing and minimizing anthracycline-induced cardiotoxicity (AIC) is a hot issue. For the treatment of AIC, calycosin (CA), an isoflavone component in astragali radix (AR), has become a research focus. However, the elaborate mechanisms of calycosin treating AIC remain to be unrevealed. Aim of the study: To explore the effects of CA on AIC through multiple dimensions concerning network pharmacology, molecular docking, and experimental evaluations. Methods: The study evaluated calycosin's potential targets and mechanisms for treating AIC using network pharmacology and molecular docking. The candidate genes/targets of CA and AIC were screened using the online-available database. Protein-protein interactions (PPI) between the common targets were constructed using the STRING platform, and the results were then visualized using Cytoscape. Molecular docking was used to evaluate the strength of the binding force between CA and the common targets. The possible pharmacological mechanisms of CA were explained by pathway enrichment and GSEA. Subsequently, the candidate targets were identified in vitro experiments. Results: Network pharmacology effectively discovered the CA's multitarget intervention in AIC, including TNF, ABCC1, TOP2A, ABCB1, and XDH. CA binds to the ATP-binding cassette subfamily B member 1(ABCB1) had the highest binding energy (-7.5 kcal/mol) according to the molecular docking analysis and was selected and visualized for subsequent analysis. In vitro experiments showed that ABCB1 exhibited significant time-curve changes under different doses of doxorubicin (DOX) compared with DMSO control experiments. The anti-AIC pharmacological mechanism of CA were revealed by highlighting the biological processes of oxidative stress (OR) and inflammation. Conclusions: We employed a practicable bioinformatics method to connect network and molecular docking to determine the calycosin's therapeutic mechanism against AIC and identified some bioinformatics results in in vitro experiments. The results presented show that CA may represent an encouraging treatment for AIC.

Efficient FMT reconstruction based on L1-αL2 regularization via half-quadratic splitting and a two-probe separation light source strategy.

Fluorescence molecular tomography (FMT) can achieve noninvasive, high-contrast, high-sensitivity three-dimensional imaging in vivo by relying on a variety of fluorescent molecular probes, and has excellent clinical transformation prospects in the detection of tumors in vivo. However, the limited surface fluorescence makes the FMT reconstruction have some ill-posedness, and it is difficult to obtain the ideal reconstruction effect. In this paper, two different emission fluorescent probes and L 1-L 2 regularization are combined to improve the temporal and spatial resolution of FMT visual reconstruction by introducing the weighting factor α and a half-quadratic splitting alternating optimization (HQSAO) iterative algorithm. By introducing an auxiliary variable, the HQSAO method breaks the sparse FMT reconstruction task into two subproblems that can be solved in turn: simple reconstruction and image denoising. The weight factor α (α>1) can increase the weight of nonconvex terms to further promote the sparsity of the algorithm. Importantly, this paper combines two different dominant fluorescent probes to achieve high-quality reconstruction of dual light sources. The performance of the proposed reconstruction strategy was evaluated by digital mouse and nude mouse single/dual light source models. The simulation results show that the HQSAO iterative algorithm can achieve more excellent positioning accuracy and morphology distribution in a shorter time. In vivo experiments also further prove that the HQSAO algorithm has advantages in light source information preservation and artifact suppression. In particular, the introduction of two main emission fluorescent probes makes it easy to separate and reconstruct the dual light sources. When it comes to localization and three-dimensional morphology, the results of the reconstruction are much better than those using a fluorescent probe, which further facilitates the clinical transformation of FMT.

Treatment of infected placenta accreta in the uterine horn by transabdominal temporary occlusion of internal iliac arteries: A case report and literature review.

RATIONALE: This case report aims to describe the treatment of infected placenta accreta in the uterine horn by transabdominal temporary occlusion of internal iliac arteries. PATIENT CONCERNS: A 29-year-old female patient had a history of retained placenta for 28 days after labor induction in the second trimester of pregnancy because of fetal malformation. DIAGNOSES: Placenta accreta in the uterine horn was diagnosed by 3-dimensional ultrasound and magnetic resonance imaging, and the diagnosis was confirmed during the operation. INTERVENTIONS: Laparotomy was performed to remove the placenta and repair the uterine defect after temporary occlusion of both internal iliac arteries. OUTCOMES: Body temperature and inflammatory markers were elevated at admission but returned to normal on the second day after surgery. Normal menstruation resumed approximately 1 month postoperatively. Ultrasound examination showed that the shape of the uterine cavity was normal. No postoperative complications were observed. LESSONS: Temporary occlusion of the internal iliac artery can help effectively manage infected placenta accreta in the uterine horn.

SCARB1 in extracellular vesicles promotes NPC metastasis by co-regulating M1 and M2 macrophage function.

Distant metastasis is currently the main factor affecting the prognosis of nasopharyngeal carcinoma (NPC), and understanding the mechanisms of metastasis and identifying reliable therapeutic targets are critical for improving prognosis and achieving clinical translation. Macrophages, as important immune cells in the tumor microenvironment (TME), have been shown to regulate metastasis. And extracellular vesicles (EVs) secreted by stromal cells and tumor cells play the important role in intercellular communication in the tumor microenvironment. However, the role of NPC-EVs on macrophages and their function in regulating macrophages to affect metastasis has not been fully clarified. In this study, we report that NPC-EVs can be uptake by macrophages and alter macrophage polarization, for the first time, we identified the genes implicated in these regulatory functions: SCARB1, HAAO, and CYP1B1. Moreover, we found that SCARB1 was positively associated with metastasis and poor prognosis of NPC. Interestingly, we found that SCARB1-rich EVs promoted M1 macrophages ferroptosis to decrease M1 macrophages infiltration by upregulating the HAAO level while decreasing phagocytosis of M2 macrophages by upregulating the CYP1B1 level. Finally, we identified the SCARB1-binding gene KLF9, which is involved in the transcription of HAAO and CYP1B1. Our findings showed that SCARB1-EVs promoted metastasis by co-regulating M1 and M2 macrophage function. The related mechanism will provide a new therapeutic strategy to help patients with NPC improve their prognosis.

Contrast-enhanced CT parameters predict short-term tumor response in patients with hepatocellular carcinoma who received sequential combined anti-angiogenesis and immune checkpoint inhibitor treatment.

PURPOSE: To evaluate whether relative Hounsfield unit attenuation index (rHUAI) on contrast-enhanced computed tomography (CECT) can predict tumor response in advanced hepatocellular carcinoma (HCC) patients who received sequential combined treatment of immune checkpoint inhibitor (ICI) and anti-angiogenesis therapy. METHOD: One hundred seventeen advanced HCC patients who underwent the sequential combined treatment in a tertiary hospital between March 2020 and December 2021 were allocated to prediction and validation cohorts (with a ratio of 2:1) based on the time of initial ICI treatment. rHUAI from the arterial to the portal-venous phase (rHU_ap) and from the portal-venous to the delayed phase (rHU_pd) was calculated. The optimal cut-off values (COVs) of rHU_ap and rHU_pd for predicting tumor response were identified using Youden's index. Univariate and multivariable analyses were performed to assess the relationship between the COVs and tumor response. The validity of COVs was verified in the validation cohort using the chi-square test and Cramer's V coefficient (V). RESULTS: The optimal COVs of the two observers were 0.5316 and 0.3265 for rHU_ap, and -0.0208 and -0.0048 for rHU_pd, respectively. Multivariable analysis suggested that the COVs were independently associated with tumor response in the prediction cohort (rHU_ap, Odds ratio: 7.727 and 7.808, 95 % CI: 2.516-23.728 and 2.399-25.410, p value < 0.001 and 0.001; rHU_pd, Odds ratio: 0.034 and 0.011, 95 % CI: 0.002-0.600 and 0.001-0.209, p value of 0.021 and 0.003). In the validation cohort, the optimal COVs of rHU_ap had a moderate to a strong association with tumor response (V = 0.362-0.545, p < 0.05). The association between COVs of rHU_pd and tumor response was slight to strong (V = 0.24-0.545, p = 0.001 to 0.134). CONCLUSION: rHUAI obtained from CECT has the potential as a non-invasive tool for predicting tumor response in advanced HCC patients who have received combined ICI and anti-angiogenesis treatment.

Pylorus-preserving versus Pylorus-resecting: Impact on dynamic changes of nutrition and body composition in pancreatic cancer patients before and after pancreatoduodenectomy.

OBJECTIVES: To investigate if different methods of pancreatoduodenectomy (with or without pyloric preservation) would have different impacts on postoperative nutrition and body composition changes among pancreatic cancer patients. METHODS: Demographic and clinicopathological data, perioperative data were collected, body composition (e.g. skeletal muscle cross-sectional area [CSA], visceral fat area [VFA]) were evaluated with abdominal CT before and after surgery. Sarcopenia patients' proportion changes were also recorded. RESULTS: The hospital stay in the PRPD group was significantly less than that in the PPPD group (p < 0.05). A significant difference was found in CSA, skeletal muscle index (SMI), VFA, VFA/CSA and albumin (ALB) in both groups between preoperative, 3, and 12 months after surgery. The loss of visceral fat in the PRPD group was more prominent than that in the PPPD group at 3 months and 12 months after surgery (p < 0.05). VFA/CSA was higher in the PPPD group than in the PRPD group (3 months: p < 0.05, 12 months: p < 0.001). The proportion of sarcopenic patients increased significantly over time in the PPPD and PRPD groups (p < 0.001). CONCLUSIONS: Postoperative CSA and VFA continued to significantly decrease in both PPPD and PRPD groups, while the incidence of sarcopenia continued to increase. Compared with PRPD, PPPD has a protective effect on visceral fat. PPPD may contribute to better maintaining visceral fat mass and blood ALB levels. CT quantification can be an objective and effective method to evaluate the nutritional status of pancreatic cancer patients during the pre- and postoperative period and can provide a useful objective basis for guiding clinical treatment.

EBV promotes vascular mimicry of dormant cancer cells by potentiating stemness and EMT.

Vascular mimicry (VM) is defined as a vascular channel-like structure composed of tumor cells that correlates with the growth of cancer cells by providing blood circulation. However, whether VM can be formed in dormant cancer cells remains unclear. Our previous research revealed that polyploid giant cancer cells (PGCCs) are specific dormant cells related to the poor prognosis of head and neck cancer. Here, we demonstrated that EBV could promote VM formation by PGCCs in vivo and in vitro. Furthermore, we revealed that the activation of the ERK pathway partly mediated by LMP2A is responsible for stemness, and the acquisition of the stemness phenotype is crucial to the malignant biological behavior of PGCCs. The epithelial-to-mesenchymal transition (EMT) process plays a considerable role in PGCCs, and EMT progression is vital for EBV-positive PGCCs to form VM. This is the first study to reveal that EBV creates plasticity in PGCC-VM and provide a new strategy for targeted anti-tumor therapy.

Bta-miR-199a-3p Inhibits LPS-Induced Inflammation in Bovine Mammary Epithelial Cells via the PI3K/AKT/NF-κB Signaling Pathway.

Mastitis is characterized by inflammatory damage to mammary gland tissue, which could decline milk production and quality and significantly affect the economic benefits of ranching. MicroRNAs (miRNAs), such as miR-199a-3p, are novel therapeutic targets in inflammation, and their regulation is an effective strategy for inflammation control. Despite its importance in humans and animals, the molecular mechanism of bovine miR-199a-3p (bta-miR-199a-3p) in dairy cow mastitis and bovine mammary epithelial cell (bMEC) inflammation is unclear. In our study, a bovine mammary epithelial cell line (MAC-T) induced by lipopolysaccharide (LPS) was used as an inflammatory cell model to investigate the molecular mechanism of bta-miR-199a-3p in the MAC-T inflammatory response. bta-miR-199a-3p was up-regulated in the LPS-induced MAC-T cells, while CD2-associated protein (CD2AP) was revealed as its target gene in a double luciferase reporter gene experiment. In addition, the overexpression of bta-miR-199a-3p negatively regulated the expression of CD2AP and the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/nuclear factor kappa-B (NF-κB) signaling pathway. These subsequently inhibited the secretion of related inflammatory factors (TNF-α, IL-1ß, and IL-6) and the expression of apoptotic genes (CASP3 and CASP9), thereby alleviating the LPS-challenged inflammatory response in the MAC-T cells. Silencing of bta-miR-199a-3p, however, reversed the above effects. Thus, bta-miR-199a-3p inhibits LPS-induced inflammation in bMECs by directly targeting CD2AP and regulating the PI3K/AKT/NF-κB signaling pathway. This study reveals the potential regulatory mechanism of bta-miR-199a-3p in bMEC inflammatory immune response and may serve as a useful target for the treatment of mastitis.

Assessing the robustness of radiomics/deep learning approach in the identification of efficacy of anti-PD-1 treatment in advanced or metastatic non-small cell lung carcinoma patients.

Administration of anti-PD-1 is now a standard therapy in advanced non-small cell lung carcinoma (NSCLC) patients. The clinical application of biomarkers reflecting tumor immune microenvironment is hurdled by the invasiveness of obtaining tissues despite its importance in immunotherapy. This study aimed to develop a robust and non-invasive radiomics/deep learning machine biomarker for predicting the response to immunotherapy in NSCLC patients. Radiomics/deep learning features were exacted from computed tomography (CT) images of NSCLC patients treated with Nivolumab or Pembrolizumab. The robustness of radiomics/deep learning features was assessed against various perturbations, then robust features were selected based on the Intraclass Correlation Coefficient (ICC). Radiomics/deep learning machine-learning classifiers were constructed by combining seven feature exactors, 13 feature selection methods, and 12 classifiers. The optimal model was selected using the mean area under the curve (AUC) and relative standard deviation (RSD). The consistency of image features against various perturbations was high (the range of median ICC: 0.78-0.97), but the consistency was poor in test-retest testing (the range of median ICC: 0.42-0.67). The optimal model, InceptionV3_RELF_Nearest Neighbors classifiers, had the highest prediction efficacy (AUC: 0.96 and RSD: 0.50) for anti-PD-1/PD-L1 treatment. Accuracy (ACC), sensitivity, specificity, precision, and F1 score were 95.24%, 95.00%, 95.50%, 91.67%, and 95.30%, respectively. For successful model robustification, tailoring perturbations for robustness testing to the target dataset is key. Robust radiomics/deep learning features, when paired with machine-learning methodologies, will work on the exactness and the repeatability of anticipating immunotherapy adequacy.

Elevated pH-mediated mitigation of aluminum-toxicity in sweet orange (Citrus sinensis) roots involved the regulation of energy-rich compounds and phytohormones.

For the first time, we used targeted metabolome to investigate the effects of pH-aluminum (Al) interactions on energy-rich compounds and their metabolites (ECMs) and phytohormones in sweet orange (Citrus sinensis) roots. The concentration of total ECMs (TECMs) was reduced by Al-toxicity in 4.0-treated roots, but unaffected significantly in pH 3.0-treated roots. However, the concentrations of most ECMs and TECMs were not lower in pH 4.0 + 1.0 mM Al-treated roots (P4AR) than in pH 3.0 + 1.0 mM Al-treated roots (P3AR). Increased pH improved the adaptability of ECMs to Al-toxicity in roots. For example, increased pH improved the utilization efficiency of ECMs and the conversion of organic phosphorus (P) from P-containing ECMs into available phosphate in Al-treated roots. We identified upregulated cytokinins (CKs), downregulated jasmonic acid (JA), methyl jasmonate (MEJA) and jasmonates (JAs), and unaltered indole-3-acetic acid (IAA) and salicylic acid (SA) in P3AR vs pH 3.0 + 0 mM Al-treated roots (P3R); upregulated JA, JAs and IAA, downregulated total CKs, and unaltered MEJA and SA in P4AR vs pH 4.0 + 0 mM Al-treated roots (P4R); and upregulated CKs, downregulated JA, MEJA, JAs and SA, and unaltered IAA in P3AR vs P4AR. Generally viewed, raised pH-mediated increments of JA, MEJA, total JAs, SA and IAA concentrations and reduction of CKs concentration in Al-treated roots might help to maintain nutrient homeostasis, increase Al-toxicity-induced exudation of organic acid anions and the compartmentation of Al in vacuole, and reduce oxidative stress and Al uptake, thereby conferring root Al-tolerance. In short, elevated pH-mediated mitigation of root Al-stress involved the regulation of ECMs and phytohormones.

Overexpression of Mitochondrial Ferritin Enhances Blood-Brain Barrier Integrity Following Ischemic Stroke in Mice by Maintaining Iron Homeostasis in Endothelial Cells.

Blood-brain barrier (BBB) breakdown, a characteristic feature of ischemic stroke, contributes to poor patient outcomes. Brain microvascular endothelial cells (BMVECs) are a key component of the BBB and dysfunction or death of these cells following cerebral ischemia reperfusion (I/R) injury can disrupt the BBB, leading to leukocyte infiltration, brain edema and intracerebral hemorrhage. We previously demonstrated that mitochondrial ferritin (FtMt) can alleviate I/R-induced neuronal ferroptosis by inhibiting inflammation-regulated iron deposition. However, whether FtMt is involved in BBB disruption during cerebral I/R is still unknown. In the present study, we found that FtMt expression in BMVECs is upregulated after I/R and overexpression of FtMt attenuates I/R-induced BBB disruption. Mechanistically, we found that FtMt prevents tight junction loss and apoptosis by inhibiting iron dysregulation and reactive oxygen species (ROS) accumulation in I/R-treated BMVECs. Chelating excess iron with deferoxamine alleviates apoptosis in the brain endothelial cell line bEnd.3 under oxygen glucose deprivation followed by reoxygenation (OGD/R) insult. In summary, our data identify a previously unexplored effect for FtMt in the BBB and provide evidence that iron-mediated oxidative stress in BMVECs is an early cause of BMVECs damage and BBB breakdown in ischemic stroke.

Pretreatment Computed Tomography-Based Machine Learning Models to Predict Outcomes in Hepatocellular Carcinoma Patients who Received Combined Treatment of Trans-Arterial Chemoembolization and Tyrosine Kinase Inhibitor.

Aim: Trans-arterial chemoembolization (TACE) in combination with tyrosine kinase inhibitor (TKI) has been evidenced to improve outcomes in a portion of patients with hepatocellular carcinoma (HCC). Developing biomarkers to identify patients who might benefit from the combined treatment is needed. This study aims to investigate the efficacy of radiomics/deep learning features-based models in predicting short-term disease control and overall survival (OS) in HCC patients who received the combined treatment. Materials and Methods: A total of 103 HCC patients who received the combined treatment from Sep. 2015 to Dec. 2019 were enrolled in the study. We exacted radiomics features and deep learning features of six pre-trained convolutional neural networks (CNNs) from pretreatment computed tomography (CT) images. The robustness of features was evaluated, and those with excellent stability were used to construct predictive models by combining each of the seven feature exactors, 13 feature selection methods and 12 classifiers. The models were evaluated for predicting short-term disease by using the area under the receiver operating characteristics curve (AUC) and relative standard deviation (RSD). The optimal models were further analyzed for predictive performance on overall survival. Results: A total of the 1,092 models (156 with radiomics features and 936 with deep learning features) were constructed. Radiomics_GINI_Nearest Neighbors (RGNN) and Resnet50_MIM_Nearest Neighbors (RMNN) were identified as optimal models, with the AUC of 0.87 and 0.94, accuracy of 0.89 and 0.92, sensitivity of 0.88 and 0.97, specificity of 0.90 and 0.90, precision of 0.87 and 0.83, F1 score of 0.89 and 0.92, and RSD of 1.30 and 0.26, respectively. Kaplan-Meier survival analysis showed that RGNN and RMNN were associated with better OS (p = 0.006 for RGNN and p = 0.033 for RMNN). Conclusion: Pretreatment CT-based radiomics/deep learning models could non-invasively and efficiently predict outcomes in HCC patients who received combined therapy of TACE and TKI.

RNA-Seq Reveals the Role of miR-29c in Regulating Inflammation and Oxidative Stress of Bovine Mammary Epithelial Cells.

Healthy mammary gland is essential for milk performance in dairy cows. MicroRNAs (miRNAs) are the key molecules to regulate the steady state of mammary gland in dairy cows. This study investigated the potential role of miR-29c in bovine mammary epithelial cells (bMECs). RNA sequencing (RNA-seq) was used to measure the transcriptome profile of bovine mammary epithelial cells line (MAC-T) transfected with miR-29c inhibitor or negative control (NC) inhibitor, and then differentially expressed genes (DEGs) were screened. The results showed that a total of 42 up-regulated and 27 down-regulated genes were found in the miR-29c inhibitor group compared with the NC inhibitor group. The functional enrichment of the above DEGs indicates that miR-29c is a potential regulator of oxidative stress and inflammatory response in bMECs through multiple genes, such as forkhead box O1 (FOXO1), tumor necrosis factor-alpha (TNF-α), and major histocompatibility complex, class II, DQ alpha 5 (BoLA-DQA5) in the various biological process and signaling pathways of stress-activated mitogen-activated protein kinase (MAPK) cascade, Epstein-Barr virus infection, inflammatory bowel disease, etc. The results imply that miR-29c plays an important role in a steady state of bMECs or cow mammary gland and may be a potential therapeutic target for mastitis in dairy cows.

Differential expression of circRNAs related to lipopolysaccharide-induced inflammation in bovine mammary epithelial cells.

Circular RNAs (circRNAs) are widely involved in inflammatory responses, but their specific regulatory roles in cow mastitis remain controversial. In this study, RNA-seq was used to generate a circRNA expression profile, which identified 71 differentially expressed circRNAs (DEcircRNAs) in lipopolysaccharide (LPS)-stimulated MAC-T bovine mammary epithelial cells (bMECs) at different stages of inflammation. Functional analyses revealed that these DEcircRNAs may be involved in cellular proliferation, apoptosis, migration, and the inflammatory responses through regulation of numerous related signaling pathways. In addition, these data suggest that 2 novel circRNAs, named novel_circ_0004830 and novel_circ_0003097, may act as the key competing endogenous RNAs (ceRNAs) in the regulation of bovine mastitis through binding to inflammation-related microRNAs (miRNAs). These results provide a new angle for the study of the molecular regulatory mechanisms in dairy cow mastitis.

Liver abscess after drug-eluting bead chemoembolization in patients with metastatic hepatic tumors.

OBJECTIVE: To investigate the incidence and risk factors for liver abscess formation after treatment with drug-eluting bead chemoembolization (DEB-TACE) in patients with metastatic hepatic tumors (MHT). METHODS: The current study is a retrospective analysis of the clinical data of 137 patients with metastatic hepatic tumors who received DEB-TACE treatment in our institute (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) between June 2015 and September 2020. Patients were evaluated for the presence or absence of post-DEB-TACE liver abscess. Univariate and multivariate analyses were used to identify risk factors for liver abscess formation. RESULTS: The incidence of liver abscess formation after the DEB-TACE procedure was 8.76% per patient and 5.53% per procedure. Univariate analysis showed that larger maximum tumor diameter (p = 0.004), Grade 1 artery occlusion (p < 0.001) and systemic chemotherapy within 3 months before the DEB-TACE procedure (p < 0.001) were all associated with liver abscess formation. However, only systemic chemotherapy within 3 months before the DEB-TACE procedure (OR 5.49; 95% CI 0.34-13.54; p < 0.001) was identified by multivariate analysis to be an independent risk factor. CONCLUSIONS: Tumor size, Grade 1 artery occlusion and recent systemic chemotherapy may all be associated with increased risk of liver abscess formation following DEB-TACE treatment in patients with metastatic hepatic tumors. ADVANCES IN KNOWLEDGE: Identification of risk factors for liver abscess formation following DEB-TACE in patients with MHT. These findings suggest the need for caution and consideration of the aforementioned risk factors on the part of interventional radiologists when designing DEB-TACE strategies and performing post-procedure patient management.

Serum-derived exosomes promote CD8+ T cells to overexpress PD-1, affecting the prognosis of hypopharyngeal carcinoma.

BACKGROUND: Hypopharyngeal cancer (HPC) is associated with a poor prognosis and a high recurrence rate. Immune escape is one of the reasons for the poor prognosis of malignant tumors. Programmed cell death ligand 1 (PD-L1) and programmed cell death-1 (PD-1) have been shown to play important roles in immune escape. However, the role of PD-1/PD-L1 in HPC remains unclear. In this experiment, we investigated the effect of exosomes from HPC patient serum on CD8+ T cell function and PD-1/PD-L1 expression and, thus, on prognosis. We hope to provide guidance for the identification of new targets for HPC immunotherapy. METHODS: PD-1 and CD8 expression in 71 HPC tissues and 16 paracarcinoma tissues was detected by immunohistochemistry. Concurrently, the clinicopathological data of the patients were obtained to conduct correlation analysis. Exosomes were isolated from serum and then identified by Western blotting (WB), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Flow cytometry was used to assess the activity of CD8+ T cells after exosome stimulation. The effects of exosomes on the ability of CD8+ T cells to kill FaDu cells were assessed by CCK-8 assay. The expression of IL-10 and TGF-ß1 was measured by enzyme-linked immunosorbent assay (ELISA). PD-L1 expression in HPC tissue samples was evaluated by immunohistochemistry, and the relationship between PD-1/PD-L1 expression and prognosis was investigated with patient specimens. RESULTS: PD-1 expression was significantly upregulated on CD8+ T cells in tumor tissues compared with those in normal tissues. The overall survival (OS) and disease-free survival (DFS) of PD-1-overexpressing patients were decreased. Serum exosomes from patients can elevate PD-1 expression on CD8+ T cells and suppress their killing capacity and secretory function. The rate of positive PD-L1 expression was increased in HPC tissues compared with paracancerous tissues. The DFS and OS of the PD-1(+)-PD-L1(+) group were significantly lower than those of the PD-1(-)-PD-L1(-) group. CONCLUSION: Our findings indicate that serum exosomes from HPC patients can inhibit CD8+ T cell function and that the PD-1-PD-L1 pathway plays an important role in the immune escape of HPC. Exosomes combined with immunotherapy may guide the treatment of patients with advanced disease in the future.

Nickel Foam Supported NiO@Ru Heterostructure Towards High-Efficiency Overall Water Splitting.

Electrocatalytic water splitting for hydrogen production from renewable energy requires the innovation of electrocatalysts with high activity and low cost. In this work, densely packed NiO@Ru nanosheets were fabricated on the surface of Ni foam through a two-step method of Ni(OH)2 growth followed by Ru deposition. Through pair distribution function analysis from selected-area electron diffraction and X-ray photoelectron spectroscopy, the interface structure feature is revealed as a thin layer of perovskite NiRuO3 sandwiched between NiO and Ru. The electrode exhibits high activity and durability for HER and OER, delivering a current density of 10 mA cm-2 at a voltage of 1.55 V for overall water splitting in 1 M KOH. The excellent performance can be attributed to the intimate interface contact of NiO and Ru in addition to low charge transfer resistance and super-hydrophilic surface structure, as verified by the electrochemical impedance spectroscopy and contact-angle measurement.

Sublethal hyperthermia enhances anticancer activity of doxorubicin in chronically hypoxic HepG2 cells through ROS-dependent mechanism.

Thermal ablation in combination with transarterial chemoembolization (TACE) has been reported to exert a more powerful antitumor effect than thermal ablation alone in hepatocellular carcinoma patients. However, the underlying mechanisms remain unclear. The purpose of the present study was to evaluate whether sublethal hyperthermia encountered in the periablation zone during thermal ablation enhances the anticancer activity of doxorubicin in chronically hypoxic (encountered in the tumor area after TACE) liver cancer cells and to explore the underlying mechanisms. In the present study, HepG2 cells precultured under chronic hypoxic conditions (1% oxygen) were treated in a 42°C water bath for 15 or 30 min, followed by incubation with doxorubicin. Assays were then performed to determine intracellular uptake of doxorubicin, cell viability, apoptosis, cell cycle, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and total antioxidant capacity. The results confirmed that sublethal hyperthermia enhanced the intracellular uptake of doxorubicin into hypoxic HepG2 cells. Hyperthermia combined with doxorubicin led to a greater inhibition of cell viability and increased apoptosis in hypoxic HepG2 cells as compared with hyperthermia or doxorubicin alone. In addition, the combination induced apoptosis by increasing ROS and causing disruption of MMP. Pretreatment with the ROS scavenger N-acetyl cysteine significantly inhibited the apoptotic response, suggesting that cell death is ROS-dependent. These findings suggested that sublethal hyperthermia enhances the anticancer activity of doxorubicin in hypoxic HepG2 cells via a ROS-dependent mechanism.

Neuropilin-1 predicts poor prognosis and promotes tumor metastasis through epithelial-mesenchymal transition in gastric cancer.

We aimed to determine whether Neuropilin-1 (NRP1) promotes gastric cancer (GC) metastasis by inducing epithelial-mesenchymal transition (EMT), and to clarify its regulatory mechanism. Using the data of GC patients in The Cancer Genome Atlas (TCGA) and Gene Tissue Expression (GTEx) databases, combined with the data of GC patients in our medical center, the effect of NRP1 on the prognosis of GC patients were analyzed. Then, we investigated the role of NRP1 in GC metastasis and its potential mechanism. The level of NRP1 was up-regulated in GC tissues and associated with poor prognosis of GC patients. The expression of NRP1 was closely related to maximum tumor diameter, invasion depth, lymphnode metastasis, distant metastasis, and advanced TNM stage, and was an independent prognostic factor for overall survival (OS) in GC patients. Besides, the results of in vitro indicated that NRP1 could induce EMT to promote the migration and invasion of GC cells by activating PI3K/Akt signaling pathway, and the HGF/c-Met axis was involved in this process. This study determined that NRP1 was a gene that promotes gastric cancer. NRP1 induced EMT to enhance the migration and invasion ability of GC cells by activating PI3K/Akt signaling pathway. NRP1 was an independent prognostic marker for OS in GC patients and expected to be a therapeutic target for GC patients.